Linked Life Data

16105836

Source:http://linkedlifedata.com/resource/pubmed/id/16105836

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
43
pubmed:dateCreated
2005-10-24
pubmed:abstractText
S134N copper-zinc superoxide dismutase (SOD1) is one of the many mutant SOD1 proteins known to cause familial amyotrophic lateral sclerosis. Earlier studies demonstrated that partially metal-deficient S134N SOD1 crystallized in filament-like arrays with abnormal contacts between the individual protein molecules. Because protein aggregation is implicated in SOD1-linked familial amyotrophic lateral sclerosis, abnormal intermolecular interactions between mutant SOD1 proteins could be relevant to the mechanism of pathogenesis in the disease. We have therefore applied NMR methods to ascertain whether abnormal contacts also form between S134N SOD1 molecules in solution and whether Cys-6 or Cys-111 plays any role in the aggregation. Our studies demonstrate that the behavior of fully metallated S134N SOD1 is dramatically different from that of fully metallated wild type SOD1 with a region of subnanosecond mobility located close to the site of the mutation. Such a high degree of mobility is usually seen only in the apo form of wild type SOD1, because binding of zinc to the zinc site normally immobilizes that region. In addition, concentration-dependent chemical shift differences were observed for S134N SOD1 that were not observed for wild type SOD1, indicative of abnormal intermolecular contacts in solution. We have here also established that the two free cysteines (6 and 111) do not play a role in this behavior.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35815-21
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16105836-Amyotrophic Lateral Sclerosis, pubmed-meshheading:16105836-Aspartic Acid, pubmed-meshheading:16105836-Binding Sites, pubmed-meshheading:16105836-Circular Dichroism, pubmed-meshheading:16105836-Copper, pubmed-meshheading:16105836-Crystallization, pubmed-meshheading:16105836-Crystallography, X-Ray, pubmed-meshheading:16105836-Cysteine, pubmed-meshheading:16105836-Disulfides, pubmed-meshheading:16105836-Dose-Response Relationship, Drug, pubmed-meshheading:16105836-Electron Spin Resonance Spectroscopy, pubmed-meshheading:16105836-Humans, pubmed-meshheading:16105836-Hydrogen Bonding, pubmed-meshheading:16105836-Ions, pubmed-meshheading:16105836-Magnetic Resonance Spectroscopy, pubmed-meshheading:16105836-Models, Molecular, pubmed-meshheading:16105836-Movement, pubmed-meshheading:16105836-Mutagenesis, pubmed-meshheading:16105836-Mutation, pubmed-meshheading:16105836-Polymerase Chain Reaction, pubmed-meshheading:16105836-Proteins, pubmed-meshheading:16105836-Spectrophotometry, pubmed-meshheading:16105836-Superoxide Dismutase, pubmed-meshheading:16105836-Zinc
pubmed:year
2005
pubmed:articleTitle
Fully metallated S134N Cu,Zn-superoxide dismutase displays abnormal mobility and intermolecular contacts in solution.
pubmed:affiliation
Magnetic Resonance Center, University of Florence, Via Luigi Sacconi 6, 50019 Sesto Fiorentino, Italy.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural